Chronic stress has been cited as a major factor in the development of substance use and dependence, including increasing vulnerability for escalation from use to abuse/dependence and relapse. One childhood stressor of particular concern is childhood maltreatment. This application requests funds to conduct secondary analyses to examine the ways in which child abuse and neglect and PTSD lead to drug use and related problems. The analyses proposed here draw upon data from a research project in which an initial sample of 908 abused and/or neglected children were matched on the basis of age, race, sex, and approximate family social class with a group of 667 non-abused and non-neglected children and followed prospectively into adulthood. The specific aims are: (1) to examine whether the child abuse and neglect leads to increased risk for drug use and abuse in adulthood; (2) to examine the association between posttraumatic stress disorder (PTSD) and drug use and abuse and the potential role of PTSD as a mediator between child abuse and neglect and drug use and abuse; (3) to examine other potential mechanisms (e.g., continuing stressors, psychosocial dysfunction, and physiological stress responsivity) which may act as mediators through which child abuse and neglect leads to drug use and abuse; (4) to examine whether certain factors (e.g., social support, hardiness, academic achievement, IQ, and reading ability) protect abused and neglected children from turning to drug use and abuse; and (5) to examine the above relationships by gender, race/ethnicity, and contextual factors. This study addresses many of the limitations of previous studies examining childhood maltreatment and drug use by using: 1) an unambiguous operationalization of abuse and neglect; 2) a prospective design; 3) separate abused and neglected groups; 4) a large sample of men and women; 5) a matched comparison group; 6) assessment of the long-term consequences of abuse and neglect beyond adolescence and into adulthood; and 7) diagnostic measures of substance use disorders and PTSD. The findings will help identify important risk and protective factors to be targeted in drug prevention/intervention programs for abused and neglected children and adolescents as well as in drug treatment programs for adult victims of maltreatment and persons with PTSD.